Antinociceptive Profile of Levo-tetrahydropalmatine in Acute and Chronic Pain Mice Models: Role of spinal sigma-1 receptor

Abstract

We have recently reported that repeated systemic treatments of extract from Corydalis yanhusuo alleviate neuropathic pain and levo-tetrahydropalmatine (l-THP) is one of active components from Corydalis. We designed this study to investigate antinociceptive effect of l-THP in acute and chronic pain models and related mechanism within the spinal cord. We found that intraperitoneal pretreatment with l-THP significantly inhibited the second phase of formalin-induced pain behavior. In addition, intrathecal as well as intraperitoneal pretreatment with l-THP reduced the mechanical allodynia (MA) induced by direct activation of sigma-1 receptor (Sig-1). In chronic constriction injury mice, these treatments remarkably suppressed the increase in MA and spinal phosphorylation of the NMDA receptor NR1 subunit expression on day 7 after surgery. Intrathecal treatment with l-THP combined with the Sig-1R antagonist, BD1047 synergistically blocked MA suggesting that l-THP modulates spinal Sig-1R activation. CatWalk gait analysis also supported that antinociceptive effect of l-THP as demonstrated by restoration of percentages of print area and single stance. Meanwhile, intrathecal pretreatment with naloxone, non-selective opioid receptor antagonist, did not affect the effect of l-THP. In conclusion, these results demonstrate that l-THP possesses antinociceptive effects through spinal Sig-1R mechanism and may be a useful analgesic in the management of neuropathic pain.

Gait Assessment of Pain and Analgesics: Comparison of the DigiGait™ and CatWalk™ Gait Imaging Systems

“…Consistent with our result, SNI CD-1 mice exhibited abnormal CatWalk ™ -duration of standing, paw intensity and print area in the ipsilateral hindpaw [ 56 ]. In another neuropathic pain model, the CCI model, CatWalk ™ explored aberrant coordination, intensity and area data [ 13 , 17 , 57 – 59 ], and the alterations in coordination and intensity correlated with punctate allodynia [ 58 ]. Compared to CCI, SNI includes complete ligations and incisions of the tibial and common peroneal nerves, and therefore induces irreversible manifestations due to motor nerve injury, for instance, the flexed ipsilateral hindpaw resulting in reduced area data.…”

Antinociceptive Effects of Isosakuranetin in a Rat Model of Peripheral Neuropathy

“…For instance, tetrahydropalmatine, a natural alkaloid from Corydalis genus Yanhusuo, has been used for the treatment of chronic pain for decades [11]. In this study, we report the potent antinociceptive effects of a natural product and TRPM 3 blocker, isosakuranetin ([2S]-5,7-dihydroxy-2-[4-methoxyphenyl]-2,3-dihydrochromen-4-one; Fig.…”

Effects of alkaloids on peripheral neuropathic pain: a review

“…Besides, brucine, koumine, gelsenicine [26], and isorhynchophylline [103] inhibited CCI-induced thermal hyperalgesia. It is reported that matrine [95], levo-tetrahydropalmatine [98], berberine [99], and sinomenine [97] could not affect the ability of spontaneous activity and motor coordination of CCI mice. In other words, these alkaloids did not induce sedation in CCI mice.…”

“…Alkaloids matrine [95] reduced among mechanical allodynia, cold allodynia, and thermal hyperalgesia, whereas guanfu base A [96] reduced mechanical and thermal hyperalgesia. Sinomenine [97], levo-tetrahydropalmatine [98], berberine [99], brucine [100], dehydrocrenatidine [101], koumine [102] and isotalatizidine [25] reduced mechanical allodynia. Besides, brucine, koumine, gelsenicine [26], and isorhynchophylline [103] inhibited CCI-induced thermal hyperalgesia.…”